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Background: The main purpose of directly sampled endometrial cytology is to detect invasive endometrial malignancies. With this principle in mind, The Yokohama System (TYS) Working Group, composed of cytopathologists, surgical pathologists, and gynecologic oncologists met at the 2016 International Congress of Cytology, Yokohama, with the aim to publish a standardized reporting system inclusive of specific diagnostic categories and cytomorphologic criteria for uniform and reliable diagnosis of endometrial malignancies on directly sampled endometrial samples. Methods: The diagnostic cytopathologic criteria previously published in the literature by the Japanese and Greek working group on endometrial cytology (Yanoh et al. [2012] Acta Cytol. 56:233; Margari et al. [2016] Diagn Cytopathol. 44:888-901) were critically reviewed with the aim of correlating the diagnostic classes to well defined risk categories for endometrial carcinoma (EC). Moreover, two classes of “atypical” endometrial cells were correlated respectively to a low- and high risk group. Some methodological suggestions for the application of ancillary special technologies to liquid based samples were also given. Results: The TYS group conceived a new Bethesda-style classification for directly sampled endometrial cytology which correlates the cytologic diagnostic classes with definite risk categories. The cytomorphologic findings have been correlated to the molecular pathology of EC, also through the application of ancillary special techniques to liquid-based samples. Conclusions: The success of TYS will depend on the acceptance of TYS by all the relevant pathology and gynecologic oncology communities who, by their joint efforts, will adopt, critically evaluate, and optimize this method with the only aim of further improving the impact of endometrial cytology on patients’ care. © 2018 Wiley Periodicals, Inc.

Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols. (Blood. 2012;120(6):1274-1281) Anaplastic large-cell lymphomas (ALCLs) are a group of clinically andbiologically heterogeneous diseases including the ALK(+) and ALK(-) systemicforms. Whereas ALK(+) ALCLs are molecularly characterized and can be readilydiagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCLare missing, and their distinction from other T-cell non-Hodgkin lymphomas(T-NHLs) remains controversial. In the present study, we undertook atranscriptional profiling meta-analysis of 309 cases, including ALCL and otherprimary T-NHL samples. Pathway discovery and prediction analyses defined aminimum set of genes capable of recognizing ALK(-) ALCL. Application ofquantitative RT-PCR in independent datasets from cryopreserved and formalin-fixedparaffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1)able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma nototherwise specified, with overall accuracy near 97%. In conclusion, our datajustify the possibility of translating quantitative RT-PCR protocols to routineclinical settings as a new approach to objectively dissect T-NHL and to selectmore appropriate therapeutic protocols

INTRODUCTION: Leptomeningeal metastases are occurring at higher frequency in cancer patients. The prognosis of leptomeningeal metastases is poor and standard treatment, which includes radiotherapy and chemotherapy, is mostly ineffective. Melanoma represents one of the tumors with the highest incidence of leptomeningeal metastases. The BRAF inhibitors have recently been demonstrated to be effective on melanoma brain metastases harboring the V600EBRAF mutation. CASE PRESENTATION: We report a case of a 39-year-old Italian woman with advanced melanoma with brain, lung and peritoneum metastases harboring the V600EBRAF mutation. In August 2010 she was enrolled into the BRIM3 trial and after the randomization process she received dacarbazine. After two cycles, there was evidence of disease progression in her peritoneum and lung. For this reason, she was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor, dabrafenib, as a second line of therapy. She had a partial response that was maintained until 13 weeks of treatment. In January 2011 she developed symptoms typical for brain metastases and received a diagnosis of leptomeningeal involvement of melanoma cells after an examination of her cerebral spinal fluid; magnetic resonance imaging was negative for meningitis or brain metastases. Analysis of her cerebral spinal fluid sample confirmed that the melanoma cells still carried the V600EBRAF mutation. After a few days, our patient went into a coma and died. CONCLUSION: Starting with a clinical case, we discuss the pathogenesis of leptomeningeal metastases and whether the leptomeninges may represent a sanctuary where melanoma cells may generate resistance and/or where BRAF inhibitors cannot reach an adequate concentration for significant activity. We assess whether treatment with BRAF inhibitors in melanoma patients should be interrupted as soon as disease progression appears or continued beyond progression through the administration of additional compounds.

Data demonstrated altered localization and expressio of galectin-3 in mesothelioma

Cytopathologic and histopathologic examination of cellular and tissue samples from serous effusions still constitute a powerful diagnostic and prognostic tool in the pathology of mesothelioma

In the present study we documented significant higher E-cadherin,beta and gamma catenin expression in non-aggressive morphological variants of differentiated thyroid cancer as compared with aggressive variants.

The receptor tyrosine kinases (RTKs) play a critical role, controlling cell proliferation, survival, and differentiation of normal cells. Their pivotal function has been firmly established in the pathogenesis of many cancers as well. The anaplastic lymphoma kinase (ALK), a transmembrane RTK, originally identified in the nucleophosmin (NPM)–ALK chimera of anaplastic large cell lymphoma, has emerged as a novel tumorigenic player in several human cancers. In this review, we describe the expression of the ALK–RTK, its related fusion proteins, and their molecular mechanisms of activation. Novel tailored strategies are briefly illustrated for the treatment of ALK-positive neoplasms.

A morphometric study was performed on the thyreocytes and Hürthle cells in 20 cases of nodular hyperplastic goiter (NHG) and in 8 cases of Hürthle cell-rich NHG. The study was carried out on cytologic samples obtained by fine needle aspiration twice from the same nodules in a selected series of patients before and after L-thyroxine therapy with the aim of evaluating the morphometric nuclear variations induced by that therapy. Thyreocytes and Hürthle cells were evaluated for nuclear Area, Perimeter, Maximum Diameter, Form Elliptic and Form Perimeter using a planimetric instrument. A statistically significant reduction in nuclear size was observed in 18 of 20 cases of NHG after L-thyroxine therapy, but the nuclear shape factors were modified only slightly or not at all. A slight reduction in the nuclear size of Hürthle cells was observed in five and an increase in the remaining three cases, but these differences were not statistically significant. Virtually no changes in shape factors were observed in this group of lesions before or after the therapy. These data are discussed and compared to the results of other series. Our results suggest that morphometry may be useful in the follow-up of NHG to evaluate the effects of L-thyroxine and that this therapy reduces the size of thyreocytes; the therapy, however, seems to have little or no effect on Hürthle cells.